This invention relates to a process for the preparation of N-[2-[4-(aminosulfonyl)phenyl]ethyl]-5-methylpyrazine carboxamide of the formula I: ##STR1## N-[2-[4-aminosulfonyl)phenyl]ethyl]-5-methylpyrazine carboxamide of the formula I is immediate or penultimate intermediate for the preparation of N-[4-(2-(5-methyl-pyrazine-2-carboxamide)-ethyl]benzene-sulphonyl]-N'cyclo hexyl)-urea which is an oral antidiabetic agent. The compound of the formula I is known to be prepared by:
(a) acetylating 2-phenylethylamine of the formula II: ##STR2## with acetic anhydride to protect the amino group and obtain N-acetyl (2-phenyl)ethylamine of the formula III: ##STR3## (b) chlorosulfonating the compound of the formula III with chlorosulfonic acid to obtain 4-(N-acetylamino) ethyl benzenesulfonyl chloride of the formula IV: ##STR4## (c) treating the compound of the formula IV with ammonia to obtain 4-(2-acetylaminoethyl)benzene sulfonamide of the formula V: ##STR5## (d) hydrolysing the compound of the formula V by treating with sodium hydroxide to deprotect the amino group and obtain 4-(2-aminoethyl)benzene sulfonamide of the formula VI: ##STR6## (e) treating the compound of the formula VI with hydrochloric acid to obtain 4-(2-aminoethyl)benzenesulfonamide hydrochloride of the formula VII: ##STR7## (f) purifying the compound of the formula VII by crystallization from methanol. PA1 (g) reprecipitating the 4-(2-aminoethyl) benzene sulfonamide of the formula VI by treating the 4-(2-aminoethyl) benzene sulfonamide hydrochloride of the formula VII with sodium hydroxide; and PA1 (h) reacting the 4-(2-aminoethyl) benzenesulfonamide of the formula VI with 5-methylpyrazine-2-carboxylic acid of the formula VIII: ##STR8## in the presence of ethyl chloroformate and triethylamine to obtain the N-[2-[4-(aminosulfonyl)phenyl]ethyl]-5methylpyrazinecarboxamide of the formula I. PA1 i) treating 5-methylpyrazine-2-carboxylic acid of the formula VIII: ##STR10## with methanol under reflux to obtain 5-methylpyrazine-2-carboxylic acid methyl ester of the formula VIII A ##STR11## ii) reacting 5-methylpyrazine-2-carboxylic acid methyl ester of the formula VIII A with 2-phenylethylamine of the formula II: ##STR12## at 100.degree. to 200.degree. C. to obtain 5-methylpyrazine 2-(2-phenylethyl) carboxamide of the formula IX: ##STR13## iii) chlorosulfonating the 5-methylpyrazine-2(2-phenylethyl)carboxamide of the formula IX with chlorosulfonic acid at 0.degree.-45.degree. C. to obtain [N-[2-[4-Chlorosulfonyl) phenyl]ethyl]-5-methylpyrazine carboxamide] of the formula X: ##STR14## iv) and treating the (N-[2-[4-(chlorosulfonyl)phenyl]ethyl]-5-methyl pyrazine-carboxamide] of the formula X with ammonia to obtain N-[2-[4-(aminosulfonyl)phenyl]ethyl]-5-methylpyrazine carboxamide of the formula I.
Due to protection and deprotection of the amino group in the 2-phenylethylamine the process involves a large number of steps and is lengthy and difficult to carry out. Yield of the process is low (of the order of 27%) because of the large number of steps. Ethyl chloroformate is toxic and creates pollution problem. 5-Methylpyrazine-2-carboxylic acid is difficult to be purified and pure acid is expensive.
The object of the invention is to provide a simple, easy, environment friendly and cheap process for the preparation of N-[2-[4-(aminosulfonyl)phenyl]ethyl]-5-methylpyrazine carboxamide of the formula I.